Imidazole → 1-Methyl-4-[1-methyl-4-[2-[4-(trifluoromethyl)phenylsulfonyl]ethoxycarbonylamino]-2-imidazolylcarbonylamino]-1H-imidazole-2-carboxylic acid ethyl ester

HRID 1883477Notes

Reaction equation

HRID 1883477 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[N:7]([CH3:14])[CH:8]=[C:9]([N+:11]([O-])=O)[N:10]=1)=[O:5])[CH3:2].N1C=CN=C1.[CH3:20][N:21]1[CH:25]=[C:24]([NH:26][C:27]([O:29][CH2:30][CH2:31][S:32]([C:35]2[CH:40]=[CH:39][C:38]([C:41]([F:44])([F:43])[F:42])=[CH:37][CH:36]=2)(=[O:34])=[O:33])=[O:28])[N:23]=[C:22]1[C:45](O)=[O:46].CN(C(F)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C>CC(=O)OCC.CN(C=O)C.C(Cl)Cl.[Pd]>[CH2:1]([O:3][C:4]([C:6]1[N:7]([CH3:14])[CH:8]=[C:9]([NH:11][C:45]([C:22]2[N:21]([CH3:20])[CH:25]=[C:24]([NH:26][C:27]([O:29][CH2:30][CH2:31][S:32]([C:35]3[CH:40]=[CH:39][C:38]([C:41]([F:44])([F:42])[F:43])=[CH:37][CH:36]=3)(=[O:33])=[O:34])=[O:28])[N:23]=2)=[O:46])[N:10]=1)=[O:5])[CH3:2]

Participants

11

Reactant 6

HCID 795ImidazoleHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2758876Ethyl 1-methyl-4-nitroimidazole-2-carboxylateHCID 2774761Tetramethylfluoroformamidinium hexafluorophosphateHCID 235107761-Methyl-4-[2-[4-(trifluoromethyl)phenylsulfonyl]ethoxycarbonylamino]-1H-imidazole-2-carboxylic acid

Product 1

HCID 207406551-Methyl-4-[1-methyl-4-[2-[4-(trifluoromethyl)phenylsulfonyl]ethoxycarbonylamino]-2-imidazolylcarbonylamino]-1H-imidazole-2-carboxylic acid ethyl esterYield 54.45%

Reagents, catalysts & solvents 4

HCID 23938PalladiumCatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

1-Methyl-4-nitroimidazole-2-carboxylic acid ethyl ester (71.05 mg, 0.3567 mmol) was dissolved in EA (10 ml) and 10% Pd/C (10 mg, catalytic weight) was added thereto. The reaction solution was stirred for 10 hours at room temperature under hydrogen atmosphere to reduce a nitro group (NO2) into an amino group (NH2), whereby an imidazole-type amino acid was obtained. 10% Pd/C was filtered out by celite 545 and the filtrate was washed with EA and methanol. 1-Methyl-4-[2-(4-trifluoromethyl-benzenesulfonyl)-ethoxycarbonylamino]-1H-imidazole-2-carboxylic acid (50.10 mg, 0.1187 mmol) dissolved in a solvent mixture of anhydrous DMF (6 ml) and DCM (2 ml) was added thereto, TFFH (94.21 mg, 0.3567 mmol), HOBt (64.74 mg, 0.4748 mmol) and DIEA (82.85 ml, 0.4748 mmol) were also added thereto, and the reaction solution was reacted according to the same procedure as Step (4-1) of Example 2 to give 1-methyl-4-({1-methyl-4-[2-(4-trifluoromethyl-benzenesulfonyl)-ethoxycarbonylamino]-1H-imidazole-2-carbonyl}-amino)-1H-imidazole-2-carboxylic acid ethyl ester (37.00 mg, 54.45%) of a pale yellow solid.

Workup

  1. customwas obtained
  2. filtration10% Pd/C was filtered out by celite 545
  3. washthe filtrate was washed with EA and methanol
  4. additionwas added
  5. customthe reaction solution was reacted

Sources & evidence

ORD record
ord-9038307f896948b084915511a3fc0681
Source dataset
uspto-grants-2004_07
Patent number
US06759511B2

Reaction notes

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